Organic-arsenic compounds

Abstract

Novel organic arsenic compounds are described as cytotoxic agents with potent anti-tumor activity against cancer cells and particularly, with regard to human leukemic cells and breast cancer cells.

We claim:  
     
       1. A compound of the formula                    
       R 1  is H, NR 3 R 4 , SR 3 , OR 3 , in which R 3  and R 4  are each independently hydrogen or a C 1 -C 4  alkyl group;  
       X is N;  
       R 2  is H, NR 3 R 4 , SR 3 , OR 3 , in which R 3  and R 4  are each independently hydrogen or a C 1 -C 4  alkyl group; or  
       a pharmaceutically acceptable salt thereof.  
     
     
       2. The compound of  claim 1 , wherein R 3  is hydrogen or methyl, and R 4  is hydrogen. 
     
     
       3. The compound of  claim 1 , wherein the compound is 2,6-Diamino-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine. 
     
     
       4. A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 1  and a pharmaceutically acceptable diluent or carrier. 
     
     
       5. A method for inhibiting the growth of tumor cells in a subject comprising administering to said subject on effective amount of a compound of  claim 1 . 
     
     
       6. The method of  claim 5 , wherein said inhibiting comprises inducing apoptosis in said tumor cells. 
     
     
       7. A method of treating cancer selected from, the group consisting of leukemia and breast cancer in a subject comprising administering to said subject a therapeutically effective amount of a compound of  claim 1 . 
     
     
       8. The method of  claim 7 , wherein said cancer is leukemia. 
     
     
       9. The method of  claim 7 , wherein said cancer is breast cancer. 
     
     
       10. A method for inducing cytotoxicity in a cell, comprising administering to said cell a cytotoxic dose of the compound of  claim 1 . 
     
     
       11. The method of  claim 10 , wherein said cell is a tumor cell. 
     
     
       12. The method of  claim 11 , wherein said compound is 
       2,6-Diamino-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine, or  
       2,6-Dimethoxyl-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine.  
     
     
       13. The method of  claim 12 , wherein said compound is 
       2,6-Diamino-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine.  
     
     
       14. A compound of the formula                    
       wherein R is                    
       R 1  is H, SR 3 , OR 3 , in which R 3  is hydrogen or a C 1 -C 4  alkyl group;  
       X is N;  
       R 2  is H, SR 3 , OR 3 , in which R 3  is hydrogen or a C 1 -C 4  alkyl group; or a pharmaceutically acceptable salt thereof.  
     
     
       15. The compound of  claim 14 , wherein the compound is 2,6-dimethoxy-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine. 
     
     
       16. A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 14  and a pharmaceutically acceptable diluent or carrier. 
     
     
       17. The pharmaceutical composition of  claim 14 , wherein the compound is 2,6-dimethoxy-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine. 
     
     
       18. A method for inhibiting the growth of tumor cells in a subject comprising administering to said subject on effective amount of a compound of  claim 14 . 
     
     
       19. The method of  claim 18 , wherein the compound is 2,6-dimethoxy-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine. 
     
     
       20. The pharmaceutical composition of  claim 4 , wherein the compound is 2,6-diamino-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine. 
     
     
       21. The method of  claim 5 , wherein the compound is 2,6-diamino-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine or 2,6-dimethoxy-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine. 
     
     
       22. The method of  claim 9 , wherein the compound is 2,6-diamino-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine or 2,6-dimethoxy-4[(4′-aminophenylazo)-phenyl arsenic acid]-1,3,5-triazine.